A reliable, highly reproducible model of bladder cancer in male Fischer rats using N-(4-(5-nitro-2-furyl)-2-thiazolyl) formamide (FANFT) has been developed. The natural history of experimental bladder cancer, patterns of invasion, dose response, and the reversibility or irreversibility of early lesions have been determined. Light, histochemical, scanning (SEM), transmission, freeze fracture, and quantitative electron microscopy of the various lesions during the course of bladder carcinogenesis were evaluated with emphasis on SEM evaluation of surface features. SEM evaluation of urinary cytology in the rat model and in humans has been developed. The presence of initiation and promotion in bladder carcinogenesis was evaluated using 0.2% FANFT for 6 weeks as initiator and either sodium saccharin or DL-Tryptophan as promoter. Both promoters significantly increased the incidence of bladder cancer in this model, but neither induced bladder tumors when fed without first feeding FANFT. Repeating this experiment but using 4 weeks of FANFT for initiation and sodium saccharin or L-Tryptophan, rather than DL-tryptophan as promoters again gave significant incidences of bladder tumors. Mild hyperplasia, but no tumors, was induced by sodium saccharin fed without FANFT prefeeding, and the effect showed a dose response. Additional studies are underway evaluating the properties of the stages of bladder carcinogenesis.